Oxidation of beta, beta-thenylhydroxylamine



Patented Mar. 8, 1949 OXIDATION {OF BETA';BETA"THEN-YL- HYDROXYLAMINE Howard D. Hartough, Pitman, N. J., assignor to Socony-Vacuum Oil Company, Incorporated, a corporation of New York No Drawing. Application'ilanuary 22, 1947, Serial No. 723,661

Claims.

The present invention relates to the preparation of oxidation products of thiophene and, more particularly, to the preparation of thiophenealdehyde, thiophenecarboxylic acid and thiophenedicarboxylic acid.

Thiophenealdehyde, according to Steinkopf, has been obtained by dry distillation of 2-thienylglyoxylic acid in a stream of carbon dioxide; Thiophenealdehyde has also been obtained by the reaction of formic acid ester and 2'-thienyl-magnesiumiodide and hydrolysis of the corresponding acetal with dilute hydrogen chloride. The aldehyde has also been obtained by passing hydrogen sulfide into an aqueous solutionof chlorodiketopentamethylene. When 2-thenoylchloride"is-reduced Withhydrogen in toluene orxylene inthe presence of palladium precipitated on bariumsulfate only about to 20 per "cent of aldehyde is obtained inaddition to the thiophenecarboxylic acid anhydride. The direct oxidation of thicphone compcunds, in general, has not-been'successful because the nuclear sulfur oxidizes-most readily with the consequentproduction of products of ring rupture. However, it now "has'been found that the oxidation of hydroxylamine derivatives of thiophene with the usual oxid-ation'reagents, permanganates, hydrogen peroxide, sodiperoxide, ammonium persulfate, potassium dichromate, dodecanoyl peroxide, benzoyl peroxide and other oxidation agents having oxidation potentials cfthe same order of magnitude-aproduces thiophenealdehyde, thiophenecarboxylic acid :and thiophenedicarboxylic.acid.

It is an object of the presentinventionfltor-provideia method for producing oxidation'products 0i thiophene byvoxidation of hydi-oxylam-i-neiderivatives of thiophene. It is another objectof the present invention to provide a method :ior producing thiophenealdehyde, thiophenecarboxylic acid and thiophenedicarboxylic acid. Other Cob-,- j ects and 'advan-ta gee will become zlapparerrt .from theeiollowing description.

in general, it has been discovered thatthiophene derivatives, particularly thiophene derivatives having an oxygen atom in a side chain and especially thiophene derivatives having an -NOI-I- group in a side chain can be readily oxidized to aldehydes and carboxylic acids by means of the usual oxidizing 'agentsusing conventional procedures. Thus;thiophenealdehyd,

thiophenecarboxylic acid and thiophenedicarboxylic acid can be obtained by oxidizing complex. amines in liquid phase with alkali metal permanganate, ammonium persulfate, alkali metal dichromate, organic peroxides, such as dodecanoyl or benzoyl peroxide, hydrogen peroxide, sodium peroxide, barium peroxide and the 'like.

Thus, for example, a complex amine whose basic structure conformsempirically to the formula:

l t 6H t vL where n is a small integerand simple amines such as di- (2-thenyl) hydroxylamine can be oxidized to produce at least one of the thiophene derivatives, thiophenealdehyde, thicphenecarb'oxylic acid and thiophenedicarboxylic acid. That is to say, when a complex amine is oxidized with a conventional oxidizing agent in the customary procedure, 2,5-thiophenedicarboxylic acid, 2-thiophenecarboxylic acidandZ- thiophenealdehyde are produced. When di-(Z- thenyl) hydroxylamine is oxidized in a similar manner Z-thiophenealdehyde and 2 -thiophenecarboxylicacid are produced. When di-(5-hydroxymethyl-2thenyl)hydroxylamine is oxidized in a similar manner only 2,5-thiophenedicarboxylic acid is produced.

Those-skilled in.the art will understand that when the side chain containing the -NOH-- group is attached tothethiophene nucleus at the 35, 4 or 5-position', the corresponding 'homologs willkbe-"obtained. Furthermore, when alkyl or other "derivatives 7 having -=one or morenuclear substituent groups in addition to an alkyl group phenecarboxylic acid (melting point 129 to 130 containing the NOH-- group are oxidized in degrees centigrade) was obtained at 128 to 129 accordance with well established oxidation prodegrees centigrade.

oedure, the corresponding derivatives of thio- From the foregoing those skilled in the art will phenealdehyde, thiophenecarboxylic acid and 5 appreciate that the novelty of the present inventhiophenedicarboxylic acid are obtained. tion does not emanate from the use of well known It is believed that the following equations repoxidizing agents and following well established resent the reactions involved: procedures for oxidation reactions but in the Illustrative of the procedure is the following exdiscovery that, in contradistinction to thiophene ample: and thiophene derivatives devoid of the --NOH A complex mixture of amines as represented by group such as dithenylamine, thiophene deriva- Formulas I to III, column 2, was prepared tives having the NOH- group attached to the by reacting about two moles of formaldoxime with thiophene nucleus through an alkyl chain can be one mole of thiophene as described in copending oxidized to aldehydes, monocarboxylic and dicarapplication for United States Letters Patent Seboxylic acids. Thus, while hydroxylamine derivarial No. 670,031, filed May 15, 1946, in the names tives of thiophene can be oxidized to aldehydes of Howard D. Hartough and Everett H. Murray, and carboxylic acids without cleavage, di-(2- Jr. Twenty parts by Weight of the amine were thenyl)amine[(C4H3S-CH2) 2NH], for example, mixed with forty parts by weight of sodium hyhaving no NOI-I group Cannot be Oxidized 0 droxide in three hundred parts by weight of thiophenealdehyde and thiophenecarboxylic acids Water and heated to boiling. Forty parts by because the heterocyclic sulfur atom is attacked weight of potassium permanganate in 300 parts in preference t the mi e oup c using rin b weight, of water r slowly dd h 2- rupture and the formation of undesirable oxidathiophenaldehyde was removed by steam distillation prod ctsc y, the present ve tion a it wa f Th thiophenaldehyde tion relates to the oxidation of thiophene comwas identified by conversion to the semicarbazone pounds containing a hydroxyla i group and which had a melting point of 218 to 219 degrees preferably corresponding t t following centigrade (uncorrected). The reaction mixture u 'i was cooled, the manganese dioxide removed by s H H s filtration and the aqueous solution evaporated to g g about one quarter (0.25) of its original volume. 5

The solution was then acidulated and the thio- H phenecarboxylic acids recovered. These acids Where R is H an alkyl group, an aryl group were recrystallized from Water once, dried and (CHZNOHCH C H Where l then digested once with hot benzene. After 0001- an alkyl or j f t'g f 0 to g $2 255 ing, the benzene solution was filtered and the m+q=3 with conventional or customar oxidz insoluble material recovered. The benzene iny I soluble material was 2,5-thiophenedicarboxylic 5 232? gigg g? szizg g g 2 23 3 32 3: acid having a neutralization equivalent of 178 m n 1k 1 p (calculated for cinzswoomz, 172). The dii ffigi fii g ig gi fif f i al-kah carboxylic acid Was converted to the dimethyl persulfate andh f oxid g fi ester by standard procedures. After recrystalliin the art will 1 nizepth t fi' t 2 Si 5 zation from methyl alcohol, the dimethyl ester beta thenylhydrox f a f be melted at 147 to 148 degrees Centigrade. (The th 1 t d y 15 use erem and m melting point given in the literature is 151 def e c i o eslgnate compounds of the general grees Centigrade. The benzene solution from ormu which the thiophenedicarboxylic acid had been removed was evaporated and the 2-thiophene- NOH carboxylic acid recovered. After recrystallization from water the 2-thiophenecarboxylic acid melted at 128 to 129 degrees centigrade. A mixed in which R and R are substituted or unsubstimelting point with an authentic sample of-2-thio 7 tuted thenyl radicals.

6 and thiophenecarboxylic acids which comprises reacting beta,beta-substituted thenyl-hydroxylamine with an oxidizing agent in alkaline solution.

5. A method of preparing thiophenealdehydes and thiophene carboxylic acids which comprises reacting a beta,beta-thenylhydroxylamine with an oxidizing agent in alkaline solution.

HOWARD D. HARTOUGH.

REFERENCES CITED The following references are of record in the file of this patent:

Acharya, Nature I36, 644 (1935). 

